DNA Sequencing for Genetic Disorders

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Disqualifiers: Dementia, Intellectual disability, Hematological cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how DNA sequencing (decoding genetic material) can improve health care by identifying genetic variants that might influence disease risk. The researchers aim to integrate this genetic information into patients' electronic health records to create a comprehensive health profile. Participants will provide a saliva sample for analysis, and those with notable genetic findings will receive counseling and recommendations for further testing. The trial seeks Mayo Clinic patients who can access the internet, provide a saliva sample, and live in the U.S., excluding New York residents. As an unphased study, this trial offers participants the chance to contribute to groundbreaking research that could enhance personalized health care.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It seems unlikely that you would need to stop, as the study focuses on DNA sequencing and not on medication effects.

What prior data suggests that DNA sequencing is safe for genetic analysis?

Research has shown that DNA sequencing is generally safe for individuals. This process examines genetic material to identify any differences. The sequencing itself poses no physical risks. However, some individuals may experience stress or worry upon discovering genetic risks, such as an increased likelihood of developing a certain disease.

Additionally, individuals might incur costs for further tests or healthcare changes based on their results. Privacy remains a concern, making it crucial to keep genetic information confidential.

Overall, while emotional and financial risks exist, DNA sequencing does not impact physical health. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about DNA sequencing for genetic disorders because it offers a personalized approach to understanding and managing genetic conditions. Unlike traditional methods that often rely on broad family history or symptom observation, DNA sequencing analyzes a person's unique genetic makeup to identify specific mutations. This can lead to earlier and more accurate diagnosis, allowing for tailored treatment plans. Additionally, the ability to share detailed genetic findings with both the participant and their healthcare provider enhances collaboration, potentially improving health outcomes. Genetic counseling and confirmatory testing provide further support, ensuring that the information is used effectively in a clinical setting.

What evidence suggests that DNA sequencing is effective for detecting genetic disorders?

Research has shown that DNA sequencing, which participants in this trial will undergo, is highly effective in diagnosing genetic disorders. For example, one study found that sequencing identified genetic problems in 52% of children with multiple birth defects affecting different body parts. Another study revealed that in 44 cases of children with unknown health issues in intensive care, 37% received a genetic diagnosis through sequencing. Importantly, in 26% of these cases, the genetic findings led to changes in the treatment plan. These results suggest that DNA sequencing can be crucial not only for diagnosing but also for improving treatment strategies for genetic conditions. ^{6 7 8 9 10}

Who Is on the Research Team?

Konstantinos N. Lazaridis, M.D.

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

This trial is for adults over 18 who can send a saliva sample from within the US, are Mayo Clinic patients with email and web access, and can consent to participate. Pregnant women may join but should consult their OB provider for prenatal genetic concerns. People with bone marrow transplants, active blood cancers, New York residency, or conditions affecting study participation (like dementia) cannot join.

Inclusion Criteria

Ability to collect and ship saliva sample within the United States

Able to provide informed written consent

I am pregnant or planning to become pregnant and understand this study doesn't replace prenatal tests.

Exclusion Criteria

Other co-morbidity which would in physician's opinion interferes with patient's ability to participate in the study (e.g., reduced ability to comprehend e.g., dementia, intellectual disability, fluency in consent language)

I have or had blood cancer.

I had a bone marrow transplant from a donor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Biospecimen Collection and Genetic Analysis

Participants receive a saliva kit, register with Helix, and undergo collection of saliva sample. Sequencing is completed by Helix, and genetic findings are shared with participants and their primary provider.

8-12 weeks

1 visit (virtual)

Genetic Counseling and Clinical Confirmation

Participants with positive results are offered genetic counseling and are encouraged to seek clinical confirmatory testing. Results are scanned into the electronic health record.

4-8 weeks

2 visits (in-person)

Follow-up

Participants are monitored for health-care utilization and acceptance of genomic testing. Medical records are reviewed, and participants are surveyed.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• DNA Sequencing

Trial Overview The trial is exploring how DNA sequencing affects healthcare by integrating genomic data into electronic health records to create a 'Health Tapestry.' It aims to identify genetic variants that could influence disease risk and improve prevention, diagnosis, or treatment.

How Is the Trial Designed?

Group I: Screening (biospecimen collection, genetic analysis) Experimental Treatment 4 Interventions

Participants receive a saliva kit, register with Helix then undergo collection of saliva sample which is returned o Helix. Participants also receive an online link to complete the About Me family history. Once sequencing is completed by Helix, ancestry/trait information and genetic findings are shared with participants and their primary provider, if applicable. Participants with positive results are offered genetic counseling and are encouraged to seek clinical confirmatory testing. Following clinical confirmation, results are scanned into the electronic health record. Participants may also undergo the collection of blood, urine, and stool samples for future studies.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

The National Institutes of Health Genetic Testing Registry (GTR) is a comprehensive online resource that provides detailed information about genetic tests available worldwide, including their purpose, methods, and validity.

The GTR allows for easy access to information about genetic testing, helping healthcare providers and patients make informed decisions about genetic disorders, as all data is voluntarily submitted and regularly updated by test providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The NIH genetic testing registry: a new, centralized database of genetic tests to enable access to comprehensive information and improve transparency. Rubinstein, WS., Maglott, DR., Lee, JM., et al.[2021]

Next-generation sequencing is revolutionizing genomic medicine by enabling faster, cheaper, and more precise genetic testing, which is particularly beneficial for diagnosing rare genetic conditions in symptomatic children.

The implementation of these advanced technologies raises important ethical issues related to test design, patient consent, and the communication of results, highlighting the need for real-world deployment to fully understand these challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genomic medicine: evolving science, evolving ethics. Soden, SE., Farrow, EG., Saunders, CJ., et al.[2021]

Next-generation sequencing (NGS) technologies allow for a more comprehensive approach to genetic diagnosis, moving from a traditional gene-by-gene method to broader techniques like diagnostic gene panel sequencing (DPS), diagnostic exome sequencing (DES), and diagnostic genome sequencing (DGS).

These NGS methods can be cost-effective for diagnosing rare genetic disorders with high variability, and they have the potential to identify new disease-related genes that were not previously associated with human diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in the Clinical Application of Next-Generation Sequencing. Ki, CS.[2021]

Next-generation gene sequencing can sequence an individual's entire genome in under a week for $5000 to $10,000, making it a promising tool for diagnosing complex diseases that are hard to identify through traditional methods.

While there have been successful applications in diagnosing diseases and improving tumor management, significant challenges remain, including data interpretation, physician training, and the need for rigorous studies to validate its effectiveness in larger patient populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The promise and challenges of next-generation genome sequencing for clinical care. Johansen Taber, KA., Dickinson, BD., Wilson, M.[2022]

Human genomic sequencing can provide valuable insights for diagnosis, prognosis, and treatment across various medical fields, but its widespread use is limited by a lack of evidence showing improved patient outcomes in those without specific testing indications.

The paper reviews clinical outcome studies in genomic medicine, highlighting the challenges of generating robust evidence to support the integration of next-generation sequencing into standard patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building evidence and measuring clinical outcomes for genomic medicine. Peterson, JF., Roden, DM., Orlando, LA., et al.[2020]

Citations

1. nature.com nature.com/articles/s41525-024-00455-3

Exome sequencing of 18994 ethnically diverse patients ... We investigated the effectiveness of exome sequencing (ES) in diagnosing ethnically diverse patients with rare genetic disorders.

2. genomemedicine.biomedcentral.com genomemedicine.biomedcentral.com/articles/10.1186/s13073-024-01301-y

Genome sequencing as a generic diagnostic strategy for rare ... We assessed whether genome sequencing (GS) can replace these existing workflows aimed at germline genetic diagnosis for rare disease.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8970663/

Lessons learned: next-generation sequencing applied to ... A study in 2017 demonstrated a diagnostic rate of 52% using singleton ES in children with multiple congenital anomalies (24). The continuing ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10899612/

Rapid genomic sequencing for genetic disease diagnosis and ... In 44 studies of children in ICUs with diseases of unknown etiology, 37% received a genetic diagnosis, 26% had consequent changes in management, ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S1098360024000029

Real-world diagnostic outcomes and cost-effectiveness of ... Using real-world data, we found earlier access to ES may yield more rapid genetic diagnosis of childhood developmental and seizure disorders and cost savings.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6143574/

Direct-to-Consumer Genomics: Harmful or Empowering? It ... Personal genomics testing can certainly determine whether a patient carries a mutant adult beta globin gene, and the clinical data concerning this gene are ...

7. medlineplus.gov medlineplus.gov/genetics/understanding/testing/riskslimitations/

What are the risks and limitations of genetic testing? There are different kinds of risks involved with genetic testing. These include physical, emotional, social, or financial.

8. cdc.gov cdc.gov/genomics-and-health/counseling-testing/genetic-testing.html

Genetic Testing | Genomics and Your Health Genetic testing looks for genetic changes, sometimes called mutations or variants, in your DNA. Some genetic changes can cause disease or other health ...

9. genome.gov genome.gov/about-genomics/policy-issues/Privacy

Privacy in Genomics This page summarizes genetic and genomic privacy in these domains, along with information on the specific laws and policies that protect the privacy of genetic ...

10. sequencing.com sequencing.com/?srsltid=AfmBOoprFSVLxGlRxRiNDNx0p9yIwj2a2HBwYeB2us6degDQnu24Temo

Genetic Testing: DNA Testing for Health, Wellness & Ancestry ... Everything you need to transform your DNA into clear solutions for better health. Whole genome sequencing kits + DNA Reports + Privacy Forever protection.